The epidemic of AIDS/HIV infection and its consequences have profoundly and irrevocably affected all aspects of biomedical science and health care practice, including dentistry. The dynamic nature of the epidemic is reflected in new populations affected, longer life spans of those with HIV infection due to retroviral therapy [HAART], and management of HIV complications, and behavioral responses among those at risk, patients and health-care providers. This continuing evolution of HIV disease is remarkably reflected in the patterns among patients, those at risk, providers and investigators in San Francisco, a city among those most affected by this disease. AIDS and HIV infection cause a wide range of serious oral lesions, or significance in the biology and natural history of HIV infection, which we have investigated for several years. This renewal application proposes a series of integrated and multi- disciplinary, yet focused and specific, studies which build on the achievements of the Oral AIDS Center at the University of California, San Francisco. The proposal is submitted by a group of clinical, epidemiological laboratory investigators which coordinated research on oral manifestations on AIDS/HIV infection has long been innovative and productive. It proposes new and technologically advanced approaches to the major questions relating to the oral lesions. We seek to understand the role of oral lesions in the context of changing therapy for the disease and the relationship of the lesions to specific host response are proposed. We seek to advance understanding of Candida albicans genes and of both Epstein-Barr virus (EBV) and host genes in hair leukoplakia by pursuing strategies that will allow examination at the cellular and molecular levels of the dynamic interactions between host and pathogen that result in disease. We thus propose a group of four integrated studies based on the unusual, perhaps unique, opportunity presented by our multi-disciplinary group to explore the interface of oral disease, epidemiology, microbiology and molecular pathology. These four coordinated and synergistic components will be supported by an administrative core and a clinical/laboratory core.